The objective of this grant proposal is an elucidation of the mechanisms by which histamine stimulates both the chronotropic and inotropic activity of cardiac muscle and a characterization of the receptor which initiates these changes in activity: a. Isolated spontaneously beating artrial muscle, driven left atrium and papillary muscle will be used to study the mechanical response of cardiac muscle to histamine, its modification by drugs and environmental conditions (ions, temperature, etc.). b. Some of the biochemical events which are initiated by receptor activation (change in calcium flux, CAMP levels, etc) will be studied during receptor stimulation, blockade and in altered metabolic states using radioactive techniques. c. A morphological study of tissue histamine compartments (cell type and intracellular location) will be done using fluorescent anatomical technique. The membrane receptor will be visualized using Sepharose bound histamine. Quantitative measurements of tissue histamine levels will be done on tissue exacts. d. Affinity chromatography will be used in an attempt to isolate the histamine receptor.